Estimating the proportion of variation in susceptibility to schizophrenia captured by common SNPs

Nat Genet. 2012 Feb 19;44(3):247-50. doi: 10.1038/ng.1108.

Abstract

Schizophrenia is a complex disorder caused by both genetic and environmental factors. Using 9,087 affected individuals, 12,171 controls and 915,354 imputed SNPs from the Schizophrenia Psychiatric Genome-Wide Association Study (GWAS) Consortium (PGC-SCZ), we estimate that 23% (s.e. = 1%) of variation in liability to schizophrenia is captured by SNPs. We show that a substantial proportion of this variation must be the result of common causal variants, that the variance explained by each chromosome is linearly related to its length (r = 0.89, P = 2.6 × 10(-8)), that the genetic basis of schizophrenia is the same in males and females, and that a disproportionate proportion of variation is attributable to a set of 2,725 genes expressed in the central nervous system (CNS; P = 7.6 × 10(-8)). These results are consistent with a polygenic genetic architecture and imply more individual SNP associations will be detected for this disease as sample size increases.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Central Nervous System / metabolism
  • Chromosomes, Human / genetics*
  • Computer Simulation
  • Female
  • Genetic Predisposition to Disease / genetics*
  • Genetic Variation*
  • Genome-Wide Association Study
  • Humans
  • Likelihood Functions
  • Linear Models
  • Male
  • Models, Genetic
  • Molecular Sequence Annotation
  • Multifactorial Inheritance / genetics*
  • Polymorphism, Single Nucleotide / genetics*
  • Schizophrenia / genetics*

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